Title |
Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells
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Published in |
European Journal of Pharmaceutical Sciences, October 2015
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DOI | 10.1016/j.ejps.2015.10.017 |
Pubmed ID | |
Authors |
Tatjana Srdic-Rajic, Katarina Nikolic, Milena Cavic, Ivana Djokic, Branislava Gemovic, Vladimir Perovic, Nevena Veljkovic |
Abstract |
Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK. Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA damaging drug doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Our data offer new insights into the pathways associated with imidazoline I1 receptor activation in K562 cells suggesting rilmenidine as a valuable tool to deepen our understanding of imidazoline I1 receptor signaling in hematologic malignancies and to search for medicinally active agents. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 20 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 5 | 25% |
Researcher | 4 | 20% |
Lecturer > Senior Lecturer | 3 | 15% |
Student > Master | 2 | 10% |
Student > Bachelor | 1 | 5% |
Other | 3 | 15% |
Unknown | 2 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 8 | 40% |
Medicine and Dentistry | 3 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 10% |
Business, Management and Accounting | 1 | 5% |
Neuroscience | 1 | 5% |
Other | 2 | 10% |
Unknown | 3 | 15% |